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Free Fatty Acids Differentially Downregulate Chemokines in Liver Sinusoidal Endothelial Cells: Insights into Non-Alcoholic Fatty Liver Disease
被引:34
|作者:
McMahan, Rachel H.
[1
]
Porsche, Cara E.
[1
]
Edwards, Michael G.
[2
]
Rosen, Hugo R.
[1
,3
,4
]
机构:
[1] Univ Colorado Denver, Div Gastroenterol & Hepatol, Dept Med, Aurora, CO 80045 USA
[2] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Dept Med, Aurora, CO USA
[3] Univ Colorado Denver, Dept Microbiol & Immunol, Aurora, CO 80045 USA
[4] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA
来源:
PLOS ONE
|
2016年
/
11卷
/
07期
关键词:
LIPID-ACCUMULATION;
INSULIN-RESISTANCE;
HEPATIC STEATOSIS;
CXC CHEMOKINE;
INJURY;
MODEL;
STEATOHEPATITIS;
RECRUITMENT;
ACTIVATION;
LIPOTOXICITY;
D O I:
10.1371/journal.pone.0159217
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Non-alcoholic fatty liver disease is a prevalent problem throughout the western world. Liver sinusoidal endothelial cells (LSEC) have been shown to play important roles in liver injury and repair, but their role in the underlying pathogenetic mechanisms of non-alcoholic fatty liver disease remains undefined. Here, we evaluated the effects of steatosis on LSEC gene expression in a murine model of non-alcoholic fatty liver disease and an immortalized LSEC line. Using microarray we identified distinct gene expression profiles following exposure to free fatty acids. Gene pathway analysis showed a number of differentially expressed genes including those involved in lipid metabolism and signaling and inflammation. Interestingly, in contrast to hepatocytes, fatty acids led to decreased expression of pro-inflammatory chemokines including CCL2 (MCP-1), CXCL10 and CXCL16 in both primary and LSEC cell lines. Chemokine downregulation translated into a significant inhibition of monocyte migration and LSECs isolated from steatotic livers demonstrated a similar shift towards an antiinflammatory phenotype. Overall, these pathways may represent a compensatory mechanism to reverse the liver damage associated with non-alcoholic fatty liver disease.
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页数:14
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